TOPICAL BENZOIC-ACID INDUCES THE INCREASED BIOSYNTHESIS OF PROSTAGLANDIN D-2 IN HUMAN SKIN IN-VIVO

Background: Benzoic acid is one of the most commonly used preservatives in cosmetics, foodstuffs, and drug preparations. Nonetheless, products containing this compound frequently induce cutaneous erythema. Previous studies have suggested that prostaglandins may mediate the cutaneous vasodilation because ingestion of cyclooxygenase inhibitors before the application of benzoic acid markedly diminishes this symptom. However, the prostaglandin responsible has not been conclusively determined. Recently we showed that cutaneous erythema similar to that associated with application of benzoic acid is induced by the topical administration of another preservative, sorbic acid, and is mediated by the increased biosynthesis of prostaglandin (PG)D-2 in the skin. This study was designed to determine whether the cutaneous vasodilation induced by benzoic acid is mediated by this prostaglandin in humans. Design: Benzoic acid (10% in petrolatum) was applied to the forearms of healthy volunteers, Blood was obtained from the antecubital vein draining the treated site and assayed for vasodilating prostaglandins and histamine. Results: Topical application of benzoic acid to four volunteers resulted in a 29- to 8000-fold increase in plasma levels of PGD(2) and a 72- to 370-fold increase in levels of 9 alpha,11 beta-PGF(2), the stable plasma metabolite of PGD,, in blood drawn from the antecubital vein draining the treated sites, In contrast, there were no changes in plasma levels of other vasodilating prostaglandins, PGE(2) or prostacyclin (PGI(2)). Increases in levels of PGD(2) and 9 alpha,11 beta-PGF(2) were not found in blood drawn simultaneously from veins in the contralateral arm, indicating the increased biosynthesis of PGD(2) from the site of benzoic acid application, Increased formation of PGD(2) in response to topical application of benzoic acid was dose dependent over a concentration range of 0.01% to 15%. The increased synthesis of PGD(2) was not accompanied by a release of histamine, suggesting that PGD(2) was not derived from the mast cell. Conclusions: PGD(2) mediates the vasodilation associated with topical application of benzoic acid.